Ceroid-lipofuscinosis neuronal protein 6 (CLN6) (CLN6)

Ceroid-lipofuscinosis neuronal protein 6 (CLN6) is a 311-amino acid, multi-pass transmembrane protein primarily localized to the endoplasmic reticulum (ER) (UniProt: P59826). It functions as part of a complex that facilitates the recruitment of lysosomal enzymes, such as cathepsin D and acid alpha-glucosidase, for transport to the Golgi apparatus (PubMed: 26831070). Mutations in the CLN6 gene cause variant late-infantile neuronal ceroid lipofuscinosis (vLINCL) and adult-onset Kufs disease type B, which are characterized by the lysosomal accumulation of ATP synthase subunit c and autofluorescent lipopigments (NIH: GeneReviews). These conditions lead to severe neurodegeneration, including symptoms like epilepsy, ataxia, and loss of vision (PubMed: 23535054). Current therapeutic development focuses on AAV-mediated gene therapy, such as AT-GTX-501, which aims to deliver a functional CLN6 gene to the central nervous system to restore lysosomal function (ClinicalTrials.gov: NCT02725580).

Other names

LinclnclfhsCLN6Neuronal ceroid lipofuscinosis 6 protein

Gene replacement therapy using an adeno-associated virus (AAV9) vector to deliver a functional copy of the CLN6 gene to the central nervous system, restoring protein function and normalizing lysosomal enzyme trafficking [ClinicalTrials.gov: NCT02725580].